The present oral toxicity study in male Wistar rats is focusing on direct and indirect thyroid toxicity. Biomaterials from this study were used to generate transcriptomics, proteomics, and metabolomics data sets. Featuring a time- and concentration-resolved design including recovery after treatment, this study allows investigating adaptive versus adverse effects in several dimensions. Two well-described test chemicals, i.e., Phenytoin and Propylthiouracil, were administered at each two dose levels to male Wistar rats for 2 (Subset A) and 4 weeks via the diet (Subset B). In addition, a recovery period of 2 weeks without test substance application was included, in order to monitor reversibility of the induced effects (Subset C). During the course of the study, blood samples were taken for metabolome analyses.